From the Editor: As the following excerpt illustrates, supramolecular
chemistry is a new chemistry, a chemistry of macromolecular
architectures and dynamics, and an exciting new interface between the
physical sciences and biology. As with any attempt to sample the work
of an entire discipline, many aspects and many researchers are
unfortunately not explicitly included. Nobel Laureate Jean-Marie Lehn
(Louis Pasteur University, FR) is one of the founders of the field.

"Today's chemists are able to understand and to make practical use of
the mutual operations of molecules both natural and synthetic. To do
so, they have had to expand their horizons, to see chemistry not just
as the science of individual molecules but also as an investigation of
how molecules come together and interact in groups -- in pairs, in
small aggregates or in vast throngs. This is the business of
supramolecular chemistry -- the chemistry beyond the molecule, the
study of ensembles of molecules working together. Only by taking a
perspective this broad can chemists hope to understand life's molecular
complexity. Yet that will be but a by-product of the supramolecular
chemist's craft. For this chemistry 'beyond the molecule' is
demonstrating that chemistry itself has a vaster potential than any
scientist of Erwin Schroedinger's generation would have guessed, a
potential whose realization will demand not just technical aptitude but
also creative imagination. It is as if the brick-makers have suddenly
realized that their products need not be an end in themselves but
provide a means for them to become architects...

"Civilization combats entropy through a network of information
exchange. (Information was made formally the opposite of entropy in
Claude Shannon's information theory in the 1940s.) We talk to each
other, we send letters, faxes and electronic mail, we write things down
and store them in libraries where others can look them up. We pass on
this information from generation to generation -- and, because it comes
mixed with a dash of inevitable disorder, it changes slowly in the
process. When molecules need to get organized, they adopt analogous
strategies. This is why the key concepts of supramolecular chemistry
embrace not just those of traditional molecular chemistry -- structure
and energy -- but also a third, information. We can regard
supramolecular chemistry as a kind of molecular sociology, wherein the
behavior of the collective results from the nature of the individuals
and the relations among them. The components of supramolecular
chemistry communicate, they form associations, they have preferences
and aversions, they follow instructions and pass on information.
Central to these exchanges is the idea of molecular recognition,
whereby one molecule is able to distinguish another by its shape or
properties."

For a long time, chemists have tried to understand nature at a level
purely molecular, considering only structures and functions involving
strong covalent bonds. But some of the most important biological
phenomena do not involve the making and breaking of covalent bonds, the
linkages that connect atoms to form molecules, Instead, biological
structures are usually made from loose aggregates held together by weak
non-covalent interactions. Because of their dynamic nature, these
interactions are responsible for most of the processes occurring in
living systems. Chemists have been slow to recognize the enormous
variety -- in terms of structure, properties, and functions -- offered
by this more relaxed approach to making chemical compounds. The slow
shift toward this new approach began in 1894, when Emil Fischer
(1852-1919) proposed that an enzyme interacts with its substrate as a
key does with its lock. This elegant mechanism contains the two main
tenets of what would become a new subject, supramolecular chemistry.
These two principles are molecular recognition and supramolecular
function. The term "supramolecular chemistry" was coined in 1969 by
Jean-Marie Lehn in his study of inclusion compounds and cryptands. The
award of the 1987 Nobel Prize in Chemistry to Charles Pedersen, Donald
Cram, and Lehn signified the formal arrival of the subject on the
chemical scene. Lehn defined supramolecular chemistry as "the chemistry
of the intermolecular bond". Just as molecules are built by connecting
atoms with covalent bonds, supramolecular compounds are built by
linking molecules with intermolecular interactions.

Nature 2001 412:397

Related Background:

SUPRAMOLECULAR ASSEMBLIES: CURRENT AND FUTURE RESEARCH

One has the sense that a renaissance in materials science is underway,
a significant refocusing with a potential impact at least as great as
that following the introduction of plastics more than a century ago. At
a recent materials science symposium on "Materials for the 21st Century
and Beyond" (April 29, Hunter College New York, US), seven leading
figures in the field presented perspectives on the near future. Nobel
Laureate Jean- Marie Lehn (Louis Pasteur University Strasbourg, FR)
reviewed the work of his group in designing and creating molecules
programmed by virtue of their structure and functional groups to
spontaneously organize themselves into larger supramolecular assemblies
held together by hydrogen bonds, metal coordination, and so on. The
interest is not so much in the mere self-assembly into large
structures, but in the fact that such self-assembled structures exhibit
a new spectrum of physical and chemical properties with important
potential practical applications. Lehn's research involves the use of
metal ions to organize and stabilize supramolecular structures with
reversible architectures, and such structures have special redox,
optical, magnetic and other properties. Michael D. Ward (University of
Minnesota Minneapolis, US) reported on the use of molecular building
blocks to construct crystalline frameworks with preordained
architectures and new functions. Ward's structures involve sheets of
organic cations and organic anions hydrogen- bonded to each other in a
hexagonal arrays. Work by other groups has involved supramolecular
multilayers. In 1988, researchers discovered that when certain films
consisting of alternating layers of a magnetic and a non-magnetic metal
are placed in a magnetic field, the resistance of the film changes
markedly, a phenomenon known as "giant magnetoresistance". This
discovery apparently reenergized the magnetic materials science field
because of important possible applications to information storage
technology, and Stuart P. Parkin (IBM San Jose, US) is now leading a
productive research group in this field. Ron Dagani (Chemical and
Engineering News), who authors a review of the symposium, concludes:
"Parkin's lecture made it clear that, at least in the case of magnetic
multilayers, some materials envisioned for the 21st century are already
here."

For over 100 years, chemistry has focused primarily on understanding
the behavior of molecules and their construction from constituent
atoms, and our current level of understanding of molecules and chemical
construction techniques has given us the confidence to tackle the
construction of virtually any molecule, be it biological or designed,
organic or inorganic, monomeric or macromolecular in origin. During the
last few decades, chemists have extended their investigations beyond
atomic and molecular chemistry into the realm of "supramolecular
chemistry". Terms such as "molecular self-assembly", "hierarchical
order", and "nanoscience" are often associated with this area of
research. In general, supramolecular chemistry is the study of
interactions between, rather than within, molecules -- in other words,
chemistry using molecules rather than atoms as building blocks. Whereas
traditional chemistry deals with the construction of individual
molecules (1 to 100 angstroms length scale) from atoms, supramolecular
chemistry deals with the construction of organized molecular "arrays"
with much larger length scales (1 to 100 nanometers). In classical
molecular chemistry, strong association forces such as covalent and
ionic bonds are used to assemble atoms into discrete molecules and hold
them together. In contrast, the forces used to organize and hold
together supramolecular assemblies are weaker non-covalent
interactions, such as hydrogen bonding, polar attractions, van der
Waals forces, and hydrophilic-hydrophobic interactions.

Proc. Nat. Acad. Sci. 2001 98:11849

4. ON NONCOVALENT
SYNTHESIS

D.N. Reinhoudt and M. Crego-Calama (University of Twente, NL) discuss
noncovalent synthesis, the authors making the following points:

1) With increasing understanding of the individual interactions that
govern the molecular recognition process, the focus is now shifting to
supramolecular chemistry as a tool for noncovalent synthesis.
Cooperative, weak interactions are used for the spontaneous formation
of large aggregates that have well-defined structures (helicates,
grids, molecular containers, capsules, cyclic arrays, and the like), in
which the individual components are not connected through covalent but
through noncovalent bonds.

2) In this emerging field of noncovalent synthesis, one might expand
the definition of a molecule to "a collection of atoms held together by
covalent and noncovalent bonds." Contrary to the classical definition
of a molecule, these supramolecules may be highly dynamic on the human
time scale. On the other hand, noncovalent and covalent synthesis are
not fundamentally different; both have as the objective to introduce
specific connectivities between atoms. The advantage of noncovalent
synthesis is that noncovalent bonds are formed spontaneously and
reversibly under conditions of thermodynamic equilibrium, with the
possibility of error correction and without undesired side products.
Furthermore, it does not require chemical reagents or harsh conditions.

3) In biosynthesis, chemical transformations are highly stereoselective
with only one of the many possible stereoisomers (compounds with the
same molecular formula that differ in the way their atoms are arranged
in space) being formed. With the current state of chemical synthesis, a
comparable stereocontrol over covalent bond formation is possible for
many types of reactions as well. In the synthesis of noncovalent
systems, this control over stereochemistry is much more difficult,
because bonds between individual components are kinetically labile and
are continuously broken and formed. However, in noncovalent synthesis,
the stereochemistry of reaction products (regioselectivity,
diastereoselectivity, and enantioselectivity) must also be controlled.

4) One of the areas where noncovalent synthesis has a great advantage
over covalent synthesis is the bottom-up (chemical) assembly of
nanostructures. Large-scale nanometer fabrication will be a requirement
for future molecular electronic devices, high-density data storage, or
drug delivery. Covalent synthesis has been proven to be extremely
fruitful for the synthesis of compounds with molecular weights in the
range of 100 to 3000 daltons such as palytoxin, norbrevetoxin, and
taxol. Nevertheless, with the exception of the sequential methodologies
for the synthesis of biopolymers (or oligomers), there are no simple
covalent strategies for the synthesis of pure molecules that have
molecular weights between 10^(4) and 10^(6) kilodaltons. Such molecules
have dimensions between 3 and 20 nanometers and fill the gap between
small molecules and larger nano-objects that are now accessible by
top-down (physical) fabrication methods, mainly based on lithography.
This is also the size range where quantum confinement influences the
electronic and optical properties of matter.

5) In summary: In chemistry, noncovalent interactions are now exploited
for the synthesis in solution of large supramolecular aggregates. The
aim of these syntheses is not only the creation of a particular
structure, but also the introduction of specific chemical functions in
these supramolecules.

1) The selective binding of a substrate by a molecular receptor to form
a supramolecular species involves molecular recognition which rests on
the molecular information stored in the interacting species. The
functions of supramolecules cover recognition, as well as catalysis and
transport. In combination with polymolecular organization, they open
ways towards molecular and supramolecular devices for information
processing and signal generation. The development of such devices
requires the design of molecular components performing a given function
(e.g., photoactive, electroactive, ionoactive, thermoactive, or
chemoactive) and suitable for assembly into an organized array.

2) Light-conversion devices and charge-separation centers have been
realized with photoactive cryptates formed by receptors containing
photosensitive groups. Electroactive and ionoactive devices are
required for carrying information via electronic and ionic signals.
Redox-active polyolefinic chains, like the "caroviologens", represent
molecular wires for electron transfer through membranes. Push-pull
polyolefins possess marked nonlinear optical properties. Tubular
mesophases, formed by organized stacking of suitable macrocyclic
components, as well as "chundle"-type structures, based on bundles of
chains grafted onto a macrocyclic support, represent approaches to ion
channels. Lipophilic macrocyclic units form Langmuir-Blodgett films
that may display molecular recognition at the air-water interface.

3) Supramolecular chemistry has relied on more or less preorganized
molecular receptors for effecting molecular recognition, catalysis, and
transport processes. A step beyond preorganization consists in the
design of systems undergoing self-organization, that is, systems
capable of spontaneously generating a well-defined supramolecular
architecture by self- assembling from their components under a given
set of conditions. Several approaches to self-assembling systems have
been pursued: the formation of helical metal complexes, the
double-stranded helicates, which result from the spontaneous
organization of two linear polybipyridine ligands into a double helix
by binding of specific metal ions; the generation of mesophases and
liquid crystalline polymers of supramolecular nature from complementary
components, amounting to macroscopic expression of molecular
recognition; the molecular-recognition-directed formation of ordered
solid-state structures.

1) Molecular electronics places a premium on organized 3- dimensional
architectures. Self-assembly has been touted as a solution to the
synthesis problems of molecular electronics. Biological self-assembly
provides striking illustrations of thermodynamically-stable
architectures, including tobacco mosaic virus, DNA, and numerous
multimeric proteins. But in many other instances biological
self-assembly is regulated in a number of characteristic ways.

2) The author introduces seven classifications of self-assembly
processes, including strict (equilibrium) self-assembly, irreversible
self-assembly, assembly following precursor modification, assembly with
post-modification, assisted assembly, directed assembly, and assembly
with intermittent processing. Strict self-assembly is governed by
equilibrium thermodynamics. The virtues of self-assembly include
minimization of information through use of modular subunits, control of
assembly and disassembly, built-in error-checking and recovery, and
overall high efficiency.

3) In many but not all instances self-assembly is a cooperative process
involving nucleation and growth phases. A fundamental theme of
cooperative assembly processes is that one series of interactions
establishes the initial structure (nucleation), thereby setting the
stage for a subsequent and more extensive series of interactions
(growth). Cooperative phenomena are well- known in biochemistry, but
cooperative assembly is not as well- developed conceptually in
synthetic chemistry.

4) A striking feature of self-assembly is that forming several bonds
can be easier than forming only one bond. Self-assembly can involve
non-covalent and covalent bond formation. Self-assembly lies at the
heart of myriad examples in chemistry, ranging from metal chelation to
model systems for self-replication. Multi- bridged cage molecules
provide one domain for comparing modern methods of one-flask syntheses
with biological self-assembly, and the syntheses of over 100 such cage
molecules are reviewed by the author. The rich precedents of biological
self-assembly may yield new paradigms for synthetic chemistry.
Molecular electronics is not alone in its requirement for controlled
3-dimensional architectures, and a deeper understanding of
self-assembly in all its manifestations is expected to benefit many
fields of chemistry.

New J. Chemistry 1991 15:15

7.
SUPRAMOLECULAR POLYMERS

"With the introduction of supramolecular polymers, which are polymers
based on monomeric units held together with directional and reversible
secondary interactions, the playground for polymer scientists has
broadened and is not restricted to macromolecular species, in which the
repetition of monomeric units is mainly governed by covalent bonding.
The importance of supramolecular interactions within polymer science is
beyond discussion and dates back to the first synthesis of synthetic
polymers; the materials properties of, e.g., nylons, are mainly the
result of cooperative hydrogen bonding. More recently, many exciting
examples of programmed structure formation of polymeric architectures
based on the combination of a variety of secondary supramolecular
interactions have been disclosed. When the covalent bonds that hold
together the monomeric units in a macromolecule are replaced by highly
directional noncovalent interactions, supramolecular polymers are
obtained. In recent years, a large number of concepts have been
disclosed that make use of these noncovalent interactions. Although
most of the structures disclosed keep their polymeric properties in
solution, it was only after the careful design of
multiple-hydrogen-bonded supramolecular polymers that systems were
obtained that show true polymer materials properties, both in solution
and in the solid state. Polymers based on this concept hold promise as
a unique class of novel materials because they combine many of the
attractive features of conventional polymers with properties that
result from the reversibility of the bonds between monomeric units.
Architectural and dynamic parameters that determine polymer properties,
such as degree of polymerization, lifetime of the chain, and its
conformation, are a function of the strength of the noncovalent
interaction, which can reversibly be adjusted. This results in
materials that are able to respond to external stimuli in a way that is
not possible for traditional macromolecules."

L. Brunsveld et al: Chem. Rev. 2001 101:4071

Related Background Brief:

SELF-COMPLEMENTARY QUADRUPLE HYDROGEN-BONDING MOTIFS AS A FUNCTIONAL
PRINCIPLE: FROM DIMERIC SUPRAMOLECULES TO SUPRAMOLECULAR POLYMERS. The
self-association of individual molecules can lead to the formation of
highly complex and fascinating supramolecular aggregates. However, for
binding motifs which rely only on hydrogen bonds, a combination of
several such weak interactions is necessary to observe self-
association in solution. Systems based on four hydrogen bonds in a
linear array can be obtained which efficiently aggregate at least in
chloroform. Besides the physical-organic characterization of these
aggregates and the factors influencing their stability, such quadruple
hydrogen-bonding motifs can also be used in the field of materials
science to synthesize, for the first time, supramolecular polymers
through the self-association of self-complementary monomers. As the
formation of noncovalent interactions is reversible and their strength
depends significantly on the chemical environment (for example,
solvent, temperature), the macroscopic properties of such polymers can
be controlled by variation of these parameters; hence a first step
towards intelligent materials with tailor-made properties is made. C.
Schmuck and W. Wienand: Angew Chem Int Ed Engl 2001 40:4363.

1) The development, characterization, and exploitation of novel
materials based on the assembly of molecular components is an
exceptionally active and rapidly expanding field. For this reason, the
topic of molecule-based materials (MBMs) was chosen as the subject of a
workshop sponsored by the Chemical Sciences Division of the United
States Department of Energy. The purpose of the workshop was to review
and discuss the diverse research trajectories in the field from a
chemical perspective, and to focus on the critical elements that are
likely to be essential for rapid progress.

2) The MBMs discussed encompass a diverse set of compositions and
structures, including clusters, supramolecular assemblies, and
assemblies incorporating biomolecule-based components. A full range of
potentially interesting materials properties, including electronic,
magnetic, optical, structural, mechanical, and chemical characteristics
were considered. Key themes of the workshop included synthesis of novel
components, structural control, characterization of structure and
properties, and the development of underlying principles and models.

3) MBMs, defined as "useful substances prepared from molecules or
molecular ions that maintain aspects of the parent molecular framework"
are of special significance because of the capacity for diversity in
composition, structure, and properties, both chemical and physical. Key
attributes are the ability in MBMs to access the additional dimension
of multiple length scales and available structural complexity via
organic chemistry synthetic methodologies and the innovative assembly
of such diverse components. The interaction among the assembled
components can thus lead to unique behavior.

4) A consequence of the complexity is the need for a multiplicity of
both existing and new tools for materials synthesis, assembly,
characterization, and theoretical analysis. For some technologically
useful properties, e.g., ferro- or ferrimagnetism and
superconductivity, the property is not a property of a molecule or ion;
it is a cooperative solid-state (bulk) property -- a property of the
entire solid. Hence, the desired properties are a consequence of the
interactions between the molecules or ions, and understanding the
solid-state structure as well as methods to predict, control, and
modulate the structure are essential to understanding and manipulating
such behaviors. As challenging as this is, molecules enable a
substantially greater ability of control than atoms as building blocks
for new materials and thus are well positioned to contribute
significantly to new materials.

5) The diversity of components and processes leads to the recognition
of the critical role of cross-disciplinary research, including not only
that between traditionally different areas within chemistry, but also
between chemistry and biochemistry, physics, and a number of
engineering disciplines. Enhancing communication and active
collaboration between these groups was seen as a critical goal for the
research area.

Advanced Materials 1998 10:1297.

9. ON
SUPRAMOLECULAR CHIRALITY

M-J. Kim et al (Kwang-Ju Institute of Science and Technology, KR)
discuss supramolecular chirality, the authors making the following
points:

1) Fundamental questions concerning chiroptical polymers arise from the
characteristics of natural polymers, which have a one-handed helical
conformation and show characteristic functionality in living
systems.(1) Conformational chirality can be optically induced by the
irradiation of photochromic molecules and polymers.(2-5) This
phenomenon has been investigated for cases of many kinds of
photochromophores, for example, azobenzenes,(2-4) overcrowded
alkenes,(5) diarylethens, binaphthalenes, and spiropyranes.

2) Since the pioneering studies by Goodman (1967), the optical
induction of supramolecular chirality has been widely studied using
azobenzene-containing polymers. Azobenzenes are well-known chromophores
for their photoinduced linear orientation via trans
cis
trans photoisomerization. Photoinduced chirality changes in azopolymers
have been reported for polymethacrylates,(2) polypeptides,(3) and
polyisocyanates.(4) These azobenzene polymers contain chiral centers,
and the chiral properties were investigated in solution using two
different wavelengths as the light source.

3) The use of circularly polarized light has been demonstrated as a
method for partially resolving a racemic mixture. Recently, Nikolova et
al (1997) reported on the photoinduced chirality of amorphous and
liquid crystalline azobenzene polymers by irradiation with circularly
polarized light. The induced chirality of the azobenzene polymers was
investigated as a function of the ellipticity of incident light.
However, Iftime et al (2000) reported that circular dichroism is not
induced in an amorphous azopolymer film by irradiation with circularly
polarized light and proposed that liquid crystalline alignment
represents one of the key factors in the creation of a chiral
superstructure. Therefore, the issue of the origin of the photoinduced
chirality of azobenzene polymer films irradiated by light with
handedness is not clear.

4) The authors report an investigation of chirality photoinduction from
amorphous and achiral azobenzene polymer films. The suggest their
results demonstrate that liquid crystallinity is not a necessary
condition for a material to exhibit photoinduced chiral properties.

1) In current polymer science, there is considerable interest in the
design of well-ordered superstructures based on self-assembly of
carefully chosen blocks. Of particular importance in this context are
noncovalent interactions, e.g., hydrogen-bonding and aromatic pi-pi
interactions. It has been demonstrated, for example, that linear
polymers and reversible networks are formed from the self-assembly of
monomers incorporating two and three 2- ureido-4-pyrimidone units,
respectively, because of the propensity of these units to dimerize
strongly in a self- complementary array of four cooperative hydrogen
bonds. But such specific interactions are not a prerequisite for a
well- controlled self-assembly: e.g., the self-assembly in bulk of
dendritic building blocks into spherical, cylindrical, and other
supramolecular architectures occurs as a consequence of both shape and
complementarity and the demixing of aliphatic and aromatic segments.

2) Despite the presence of considerable order on different length
scales, single crystals suitable for diffraction studies, and thus full
crystal structures, are not available for such self- assembled
supramolecular entities. If the mechanisms governing self-assembly are
to be better understood, analytical methods capable of probing the
structure and dynamics of these partially ordered systems are
essential. In recent years, the field of solid-state nuclear magnetic
resonance (NMR) has enjoyed rapid technological and methodological
development, and advanced solid- state NMR methods are currently well
placed to meet the challenge of modern polymer chemistry. In
particular, with such methods much insight can be achieved with small
amounts (10 to 20 milligrams) of as-synthesized samples.

Chem. Revs. 2001 101:4125

11. ON
THE ENGINEERING OF SUPRAMOLECULAR CRYSTALS

T.L. Nguyen et al (State University of New York Stony Brook, US)
discuss supramolecular crystal engineering, the authors making the
following points:

1) Crystal engineering (in this context, supramolecular synthesis) is
an important problem that requires a detailed knowledge of
intermolecular interactions. One would like to be able to choose
appropriate molecules or sets of molecules and predict with confidence
the manner in which they will crystallize. This is a difficult problem
of great complexity, and indeed in many cases there may be no simple
thermodynamic basis for a successful prediction. Crystallization is a
kinetic process, and polymorphism often appears when it is most
inconvenient. The authors suggest that chemists persevere with a
certain confidence that by a clever design they will achieve the
structural result they seek. Success is achieved either by wisely
setting limited structural goals in the first place, or by making
judicious use of ex post facto crystal design.

2) Despite these difficulties, one can still imagine a scenario where
one could reliably predict the total structure of a crystal purely on
the basis of knowledge of molecular properties. Total structure
prediction would require specification of molecular geometry and
orientation, unit cell dimensions, and the space group. The authors
report that their simplified approach to this problem has been to
identify molecular functionalities that will predictably and
persistently lead to crystals containing defined network structures.
Each chosen functionality has a size and shape that leads to
characteristic repeat distances within its networks, and these
molecular networks are substructures of the final crystal. The networks
have repeat distances commensurate with the unit cell of the crystal,
and their group symmetries are a subgroup of the space group of the
final crystals. The distance parameters can be predicted, and a
consideration of molecular symmetry combined with the symmetry of each
anticipated intermolecular bond can lead one to the correct network
symmetry. The authors state: "By combining good chemical insight with
solid crystallographic principles, one can design or engineer
crystalline solids that contain networks with desired structural
features."

J. Am. Chem. Soc. 2001 123:11057

12. ON
THE HISTORY OF CRYSTAL ENGINEERING

In general, in this context, "goniometry" involves the measurement of
interfacial angles for the comparison of crystals of different
development. William Wollaston (1766-1828) developed in 1809 a
reflecting (optical) goniometer for use with small crystals: a fixed
mirror is illuminated from a collimator so that part of the parallel
beam falls on the crystal, which is fixed on an axis parallel to the
mirror and a short distance above it, and is so adjusted that the edge
of the facial angle to be measured is parallel to the axis. All the
interfacial angles in a given zone can be found by rotation of the
crystal.

Mark D. Hollingsworth (Kansas State University, US) discusses the
history of crystal engineering, the author making the following points:

1) Legend has it that modern crystallography owes its roots to an
accidental discovery reported in 1781 by the French physicist Rene Just
Hauey (1743-1822) (1). While admiring a friend's mineral collection,
Hauey dropped a particularly large crystal of Iceland spar (calcite),
which cleaved into equivalent fragments. With keen insight, Hauey
recognized that internal structure was related to external form, and
after spending the next years smashing his mineral collection and those
of his friends, he reckoned that all crystals were composed of a
limited number of building blocks that were stacked together in simple
ways. With the subsequent development of optical goniometry, polarized
light microscopy, and other physical techniques, 19th-century chemists
and crystallographers focused on macroscopic properties of crystals
such as birefringence, optical activity, pyroelectricity (electric
polarization caused by temperature change), and, later,
piezoelectricity (electric polarization under external stress), which
was discovered by Pierre and Jacques Curie in 1880. These efforts
culminated in Paul Groth's Chemische Krystallographie (2), which
documents in five volumes what was known about the external form and
physical properties of more than 7000 organic and inorganic crystals
that had been characterized by the beginning of the 20th century.

2) Groth's treatise and Hauey's deconstruction of macroscopic
crystalline objects provide instructive contrasts with the modus
operandi of modern-day solid state organic chemists and "crystal
engineers", who have embraced the notion of the supramolecular
"synthon" (3) as the critical design element for generating new
materials. In its renaissance, as inaugurated by G.M.J. Schmidt and
coworkers in the 1960s (4), solid state organic chemistry has focused
on the molecular building blocks and their connections with the
anticipation that reliable functional group interactions can be used to
assemble a variety of useful molecular materials.

3) The synthesis of organic molecules relies on the strength of
covalent bonds and on the relative rates of bond-forming processes to
lead in a rational and step-wise process to the final product. It is
therefore no surprise that many organic chemists have until recently
shied away from crystal synthesis. For the supramolecular synthetic
chemist, the specific goal is a macroscopic property, and the final
product is often a moving target that changes each time the crystal
synthesis yields something different from that predicted by the
imperfect models we use. The fundamental difficulty for this field is
that molecular crystals are held together by a multitude of weak
interactions, and a huge number of free energy minima (polymorphs)
exist within a few kilojoules/mol of the global minimum. The process of
crystal engineering is therefore an iterative one that involves
synthesis, crystallography, crystal structure analysis, and
computational methods.(5)

C.M. Drain et al (City University of New York, US) discuss porphyrin
arrays, the authors making the following points:

1) With the increasing demand for the ability to sculpt matter into
precise functioning devices of nanoscale dimensions, the molecular
level design of functional materials is an overarching theme in much of
the synthetic materials literature (1-5). Inspired by biological
systems, the introduction of specific interactions is a route toward
using the facile and energetically favorable production capabilities to
self-assemble materials. Exploitation of nonspecific intermolecular
interactions has resulted also in the formation of molecular electronic
devices.

2) The authors report they have used self-assembly to form a square
planar array of nine porphyrins mediated by coordination of exocyclic
pyridyl groups on three different porphyrins to 12 trans-palladium
dichlorides. In addition to modulating the size and distribution on
surfaces, metalation of the porphyrin macrocycle enables one to design
nanoscale systems with a host of photonic, magnetic, redox catalytic,
and sensor capabilities. These functions have been well studied on
metalloporphyrin monomers. Substitution of the peripheral R groups with
long-chain hydrocarbons enables the design of nanoscale aggregates
that, using nonspecific interactions, organize into two-dimensional
arrays. The authors present an overview of the design capabilities for
materials and devices by using porphyrin supramolecular arrays.

3) In summary: The authors report that tessellation of nine free- base
porphyrins into a 3 ž 3 array is accomplished by the self- assembly of
21 molecular entities of four different kinds, one central, four
corner, and four side porphyrins with 12 trans Pd(II) complexes, by
specifically designed and targeted intermolecular interactions.
Strikingly, the self-assembly of 30 components into a metalloporphyrin
nonamer results from the addition of nine equivalents of a first-row
transition metal to the above milieu. In this case each porphyrin in
the nonameric array coordinates the same metal such as Mn(II), Ni(II),
Co(II), or Zn(II). This feat is accomplished by taking advantage of the
highly selective porphyrin complexation kinetics and thermodynamics for
different metals. In a second, hierarchical self-assembly process,
nonspecific intermolecular interactions can be exploited to form
nanoscaled three-dimensional aggregates of the supramolecular porphyrin
arrays. In solution, the size of the nanoscaled aggregate can be
directed by fine-tuning the properties of the component macrocycles, by
choice of metalloporphyrin, and the kinetics of the secondary
self-assembly process. As precursors to device formation, nanoscale
structures of the porphyrin arrays and aggregates of controlled size
may be deposited on surfaces. Atomic force microscopy and scanning
tunneling microscopy of these materials show that the choice of surface
(gold, mica, glass, etc.) may be used to modulate the aggregate size
and thus its photophysical properties. Once on the surface the
materials are extremely robust.

OPTIMIZATION AND CHEMICAL CONTROL OF PORPHYRIN-BASED MOLECULAR WIRES
AND SWITCHES. Porphyrin molecular wires consist of porphyrin units
fused to acene-type bridges and have been synthesized by the authors in
a range of topologies including linear porphyrin octamers of length ca.
120 ?. The authors demonstrate, for some linear oligoporphyrins, how
the electronic coupling between the end porphyrin units can be
modulated by simple (possibly in situ) chemical modulation of the
bridging units. Specifically, the chemical systems considered involve
either pH-controlled protonation of bridge azines or conversion of
bridge quinone or quinone dioxime rings to or from benzenoid or
hydroquinone rings. In the most general terms, the electronic coupling
through oligoporphyrin molecular wires is discussed in terms of a
simple model in which complete end-to-end electronic delocalization is
required in order to provide strong long-range interactions.
Computationally, the authors monitored interorbital coupling using an
appropriate mixture of density functional and ab initio SCF
computational schemes. Finally, the authors examined bridge modulation
of the intermetallic coupling in three homovalent bis-metallic
oligoporphyrin systems. Results were obtained both using an effective
two-level model, appropriate for spectroscopic properties, and using a
more general scheme, appropriate for molecular conduction. N.S. Hush et
al: Ann New York Acad Sci 1998 852:1.

Related Background Brief:

SELF-ORGANIZATION OF SELF-ASSEMBLED PHOTONIC MATERIALS INTO FUNCTIONAL
DEVICES: PHOTO-SWITCHED CONDUCTORS. Linear porphyrin arrays
self-assembled by either hydrogen bonding or metal ion coordination
self-organize into lipid bilayer membranes. The length of the
transmembrane assemblies is determined both by the thermodynamics of
the intermolecular interactions in the supramolecule and by the
dimension and physical chemical properties of the bilayer. Thus, the
size of the porphyrin assembly can self-adjust to the thickness of the
bilayer. An aqueous electron acceptor is placed on one side of the
membrane and an electron donor is placed on the opposite side. When
illuminated with white light, substantial photocurrents are observed.
Only the assembled structures give rise to the photocurrent, as no
current is observed from any of the component molecules. The
fabrication of this photogated molecular electronic conductor from
simple molecular components exploits several levels of self-assembly
and self-organization. Charles M. Drain: pnas 2002 99:5178.

14. ON
HYDRATED AMPHIPHILES AND SUPRAMOLECULAR MATERIALS

In general, "amphiphiles" are molecules with parts (groups) having
diverse affinities for different solvents. For example, polar groups
have an affinity for water, while hydrocarbon groups have an affinity
for oils. Most detergents are amphiphiles, molecules with a polar head
and a long hydrocarbon tail. In this context, however, possible solvent
interactions are only one aspect of amphiphilic character. The
important consideration is that amphiphiles tend to self-organize:
groups of amphiphilic molecules will form stable domains of polar
interactions and nonpolar interactions. For example, amphiphiles may
form "micelles", spherical or cylindrical arrangements with an interior
forming one interaction domain while the surface forms another
interaction domain. Larger aggregates may form vesicles with diameters
in the micron range.

A simple linear polymer is a chain molecule composed of monomers with
two reactive sites (bifunctional monomers), with monofunctional
terminal units. If more than one bifunctional monomer is present, the
chain is known as a "copolymer". A copolymer in which a number of units
of the same monomer are located adjacent to one another (in "blocks" of
monomers) is called a "block copolymer". A "diblock copolymer" is
composed of two types of monomers (e.g., A and B), and may be depicted
thus: AAAAAABBBBBAAAAAABBBBBAAAAAAA.

In general, a "homopolymer" is any polymer made up of only one kind of
constitutional repeating unit, e.g., cellulose, which contains only
glucose as the monomeric unit.

A "Langmuir-Blodgett film" (Langmuir-Blodgett multilayer) is a film of
molecules on a solid surface, the film with multiple layers made by
dipping a plate into a liquid so that it is covered by a monolayer and
then repeating the process. The technique enables a multilayer to be
built up one monolayer at a time, and such layers have many practical
applications.

A. Mueller and D.F. O'Brien (University of Arizona, US) discuss
hydrated amphiphiles, the authors making the following points:

1) Hydrated amphiphiles form various phases as a function of molecular
structure, temperature, concentration, and pressure.(1- 4), and there
appears to be a one-to-one correspondence between the structures
observed for hydrated amphiphiles and that for block copolymer.(5)
Amphiphiles are characterized by having a hydrophilic headgroup
attached to at least one hydrophobic tail. The unfavorable interfacial
enthalpic interaction between the hydrophobic tail(s) of the amphiphile
with the polar water molecules induces the former to aggregate with the
hydrophobic tail(s) of other amphiphiles.(4) The hydrophilic headgroup
therefore separates the water from the tail(s), in much the same way
that the A-B junction of a diblock AB copolymer separates the two
homopolymer blocks A and B. Self-organized arrays of noncovalently
associated amphiphiles may exist as self-supported lamellar/vesicular,
various bicontinuous cubic, or hexagonal/cylindrical phases.
Amphiphiles are also frequently studied as supported assemblies, e.g.,
monolayers at the air- water interface, Langmuir-Blodgett, or
self-assembled monolayers. During the past two decades or so, the
understanding of each of these supramolecular assemblies has advanced
significantly. This progress is a consequence of fundamental and
applied research in many laboratories.

2) The advent of methods to polymerize supramolecular assemblies, first
in monolayers in the 1970s, followed by bilayer vesicles in the early
1980s, and more recently in nonlamellar phases, i.e., cubic and
hexagonal phases, has led to the creation of new materials, the
development of new methods, and a widening perspective on the potential
applications of these novel polymeric materials. These uses include the
controlled delivery of reagents and drugs, the preparation of
biological membrane mimics, the separation and purification of
biomolecules, the modification of surfaces, the stabilization of
organic zeolites, and the preparation of nanometer colloids, among
others.

3) The concept of an area-minimizing surface has been used extensively
to describe the morphologies of amphiphile/water systems.(2) The free
energy of the system is described by the topology of the surfaces. In
such an analysis, a spontaneous curvature term arises purely as a
result of the fact that the dimensions of the microdomain are only a
few orders of magnitude greater than that of the constituent molecules.
This means that the shape of the interface is influenced by the
interactions on a molecular level. In order for a system to achieve
equilibrium, the various terms in the free energy expression, chief of
which is the mean curvature, must be minimized. This theory has been
extended to describe the effects of surface charge and branched alkyl
chains on the formation of nonlamellar assemblies. The distribution of
a mixture of lipids in nonlamellar phases has also been investigated.

S. Zeena and K.G. Thomas (Regional Research Laboratory, IN) discuss
photoactive chemical systems. The design and study of molecular and
supramolecular photoactive systems have been actively pursued in recent
years due to their potential applications in optoelectronic devices
(e.g., molecular switches, sensors, transducers, and information
processing and storage devices). Of particular interest is the design
of molecular systems which undergo conformational changes analogous to
the folding of proteins. Synthetic molecular systems and polymers which
can fold into well-defined conformation in solution ("foldamers")
through non-covalent interactions have been reported. These include 1)
solvophobically driven conformational folding of phenyacetylene-based
oligomers into ordered helical structures, and 2) the donor-acceptor
interaction or aromatic groups leading to pleated structures.
Conformational changes and molecular motions in photoactive molecular
and supramolecular systems can be modulated by chemical, photochemical,
or electrochemical methods, and such changes, when translated into
optical or electronic properties, can form the basis of switching
devices. The authors report they have designed two nonconjugated
bichromophores which can fold and unfold by varying the solvent
polarity or by the application of external stimuli such as heat or
light.

J. Am. Chem. Soc. 2001 123:7859

16. METAL-COORDINATION
IN SUPRAMOLECULES

C.J. Kuehl et al (University of Utah, US) discuss metals in
supramolecules. Over the past decade, the use of metal coordination as
a means to drive and preserve the formation of discrete molecular
ensembles has become an established methodology in supramolecular
chemistry. However, the level of complexity to which metal-mediated
self assembly can develop as a general synthetic strategy has yet to be
realized. Nevertheless, the design and construction of new
supramolecular entities refine our understanding of the fundamental
principles of molecular self-organization. So far, highly symmetric
ring systems (e.g., molecular triangles, squares, pentagons, hexagons,
etc.) have generally been the most successfully characterized species,
because of their inherent simplicity over three-dimensional constructs.
Typically comprising aromatic bridging ligands connected via transition
metals, these "metallocyclophanes" have shown promise as a new class of
functional receptor molecules that can act as hosts in host-guest
complexes. Considering that metal-containing macrocycles often possess
magnetic, photophysical, and/or redox properties not accessible from
purely organic systems, studies in basic host-guest chemistry have
broad implications for technologies such molecular sensing,
separations, and catalysis. However, precise size and highly specific
electrostatic and dispersion forces are required for selectivity, and
for the most part this remains an important challenge for research.

J. Am. Chem. Soc. 123:9634

17. SELECTIVE ASSEMBLY OF
SUPRAMOLECULAR AGGREGATES

Y. Yokoyama et al (National Institute for Materials
Science, JP)
discuss selective assembly of supramolecular aggregates on a surface.
The realization of molecule-based miniature devices with advanced
functions requires the development of new and efficient approaches for
combining molecular building blocks into desired functional structures,
ideally with these structures supported on suitable substrates.
Supramolecular aggregation occurs spontaneously and can lead to
controlled structures if selective and directional non-covalent
interactions are exploited. But such selective supramolecular assembly
has yielded almost exclusively crystals or dissolved structures. In
contrast, the self-assembly of adsorbed molecules into larger
structures has not yet been directed by controlling selective
intermolecular interactions. The authors report the formation of
surface-supported supramolecular structures whose size and aggregation
pattern are rationally controlled by tuning the non-covalent
interactions between individual adsorbed molecules. Using
low-temperature scanning tunneling microscopy, the authors demonstrate
that substituted porphyrin molecules adsorbed on a gold surface form
monomers, trimers, tetramers, or extended wire-like structures. The
authors report that each structure corresponds in a predictable fashion
to the geometric and chemical nature of the porphyrin substituents that
mediate the interactions between individual adsorbed molecules. The
authors suggest their findings indicate that careful placement of
functional groups that are able to participate in directed non-covalent
interactions will allow the rational design and construction of a wide
range of supramolecular architectures adsorbed to surfaces.

Nature 2001 413:619

18.
SUPRAMOLECULES AND BIOLOGICAL MOVEMENTS

Directed motion is one of the more dramatic characteristics of many
living systems, and the movements of simple organisms, particularly of
single-celled organisms, have fascinated biologists ever since the
invention of the microscope. Under a microscope, a motile protozoan may
appear as large as a rabbit, but there are no muscles or nerves in the
single cell that constitutes such an organism, and the riddle is clear:
How is chemical energy transduced to directed mechanical and kinetic
energy in primitive biological systems? Until the era of the electron
microscope and molecular biology, little progress was made in answering
this question. That has changed: in recent decades molecular biology
has provoked a renaissance in studies of cell movements. But if much
has been learned and the questions refined, our fascination with motion
in primitive organisms has grown rather than diminished. For it has
become apparent that directed motions in primitive biological systems
are examples of molecular-scale engineering that is often astonishing.
Vorticella, discussed below, is a ciliated protozoan common in ponds, a
single-celled organism that can be envisioned as follows: Imagine a
bell-shaped body 50 microns at its widest part. The rim of the open end
of the bell is covered with cilia that beat synchronously to sweep
water and nutrients into the open end of the body. The closed dome end
of the bell is attached to a long thin stalk that may be 500 or more
microns in length, and the far base of the stalk is attached to a leaf
or to pond debris. When the organism is feeding, the stalk is extended.
When the organism is physically or chemically disturbed, the stalk
contracts like a spiral-shaped spring, quickly drawing the bell- shaped
body of the organism to the protection of the debris where it is
attached. First described by Anton van Leeuwenhoek (1632-1723),
Vorticella is a legendary organism in biology. Many children receive
inexpensive microscopes as gifts when they are ten or eleven years old,
and these children often use their new microscopes to examine
everything available, including local pond water. At the first sight of
Vorticella -- the lovely bell-shaped body with its synchronously
beating cilia, the body at intervals suddenly pulled back by the
contracting spring of the stalk, the stalk and body then slowly
extending again with the cilia resuming their synchronized beating --
such children are often spellbound by the dynamic world of the small.
If the fascination endures, and if they are fortunate in life, they
often become biologists.

L. Mahadevan and P. Matsudaira (Massachusetts Institute of Technology,
US) present a review of recent research on cell motility, the authors
making the following points:

1) The retraction of the stalk of Vorticella (and of other ciliates of
this type: peritrich ciliates) is caused not by the sliding action of a
motor protein but by a spring that operates according to a simple
mechanism: the entropic collapse of polymeric filaments. Although they
are considered unusual engines for motility, springs and ratchets
composed of filaments and tubules power many of the largest, fastest,
and strongest cellular and molecular movements. Just as muscles magnify
forces and movements by a geometrical hierarchy, these unusual
mechanochemical engines use a similar principle: small changes in a
protein subunit are amplified by the linear arrangement of proteins in
filaments and bundles. The authors suggest that, considering the
biochemical and physical characteristics of several known molecular
springs and ratchets, they apparently represent ancient and
biologically commonplace molecular engines.

2) In general, biological springs are active mechanochemical devices
that store the energy of conformation of proteins in certain chemical
bonds that act as latches. In the absence of an external force, the
potential energy is released and converted into mechanical movement
when the chemical bonds are broken.

3) The contractile avoidance reaction of Vorticella, first described by
Leeuwenhoek in 1676, is a dramatic example of an active mechanochemical
spring. The body of Vorticella is attached to a leaf or to debris by a
long slender stalk. Within the stalk lies a rod-like helical
cytoplasmic organelle, the "spasmoneme". In its extended state, the
spasmoneme is 2 to 3 millimeters long, depending on the species of
ciliate. When exposed to calcium ions, but to no external energy
source, the spasmoneme contracts in a few milliseconds to 40 percent of
its length at velocities approaching 8 centimeters per second. Based on
the hydrodynamics, the force of contraction is of the order of a
millidyne, whereas the power generated is a few milliergs per second.
In terms of specific power per unit mass, the spasmoneme is among the
most powerful biological engines.

4) The authors state: "The dynamics and energetics of biological
springs and ratchets are dominated by factors that are inconsequential
on the large length scales associated with our everyday world. In a
[biological] cell, viscous forces, Brownian motion, short-range
hydrophobic interactions, screened electrostatics, and steric effects
influence the kinetics of filament and subunit diffusion and growth. In
this soft, wet, and dynamic world, structural features are dominated by
filamentous and membranous objects, a constant reminder that all events
at this level are mediated by interfacial interactions."